In the etiology of diabetes the strength and character of the genetic influences have been poorly defined. Among the main reasons for this are the inadequacies of the data collected, particularly those concerning the present and previous fatness of both probands and family members. In a whole population of Indian adults in which diabetes and obesity are rife, a study is proposed in which data collection would be uniquely complete, including information on glucose tolerance and both present and previous adiposity on all available adults (about 3,200). This will include about 700 with fasting hyperglycemia and several hundred more with varying degrees of impairment of glucose tolerance. Propitious circumstances include the large families, the geographic proximity of family members, and a centralized record system that provides information (on weight and other data) extending over the past 40 years. This will allow a determination of the inter-relationships of obesity and heredity, including an assessment of the extent to which the familial aggregation of maturity-onset diabetes is secondary to the familial aggregation of obesity. Another aspect of the study will be a comparison of familial patterns of insulin-independent diabetes of obese and insulin-dependent diabetes of the lean. In diabetes the extent to which there is familial concordance of susceptibility to retinopathy will be examined. Other observations will be designed to confirm that juvenile-onset diabetes is rare in Oklahoma Indians, and to explore possible causes of the paucity.